The emergence of pressurized intraperitoneal aerosol chemotherapy as a palliative treatment option for patients with diffuse peritoneal metastases: a narrative review

Lurvink, Robin J.; Speeten, Kurt Van der; Rovers, Koen P.; Hingh, Ignace H. J. T. de

doi:10.21037/jgo-20-497

Cited by 16 publications

(15 citation statements)

References 72 publications

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“…Currently, the only nozzle specifically approved for IP aerosol delivery is a single fluid, high pressure atomizer (CapnoPen, Capnomed, Zimmern, Germany), which sends therapeutic solutions at an elevated pressure of maximally 20 bar through a 200 μm sized orifice. , However, this device produces aerosols with a relatively large droplet size and high momentum, leading to a suboptimal aerosol distribution due to gravitational effects . To improve the IP distribution homogeneity of nebulized formulations, a multidirectional nozzle for aerosolization of viscous materials was developed in collaboration with Medspray.…”

Section: Introductionmentioning

confidence: 99%

“…By exploiting the advantages of a fine, hovering aerosol and an elevated abdominal pressure, PIPAC intends to improve the peritoneal drug distribution and tissue uptake compared to liquid instillation of formulations. An additional advantage of this minimally invasive technique is its repeatability. , To further optimize the distribution homogeneity and tumor penetration of aerosolized liquids, electrostatic precipitation PIPAC (ePIPAC) has been developed. Here, a generator is connected to the patient, which confers a negative charge to the aerosol droplets and positive charge on the IP tissues, leading to electrostatic aerosol precipitation, thereby counteracting the effects of gravity and drag. , …”

Section: Introductionmentioning

confidence: 99%

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CO₂-Driven Nebulization of pH-Sensitive Supramolecular Polymers for Intraperitoneal Hydrogel Formation and the Treatment of Peritoneal Metastasis

Braet,

Fransen,

Mariën

et al. 2023

ACS Appl. Mater. Interfaces

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Because peritoneal metastasis (PM) from ovarian cancer is characterized by non-specific symptoms, it is often diagnosed at advanced stages. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) can be considered a promising drug delivery method for unresectable PM. Currently, the efficacy of intraperitoneal (IP) drug delivery is limited by the off-label use of IV chemotherapeutic solutions, which are rapidly cleared from the IP cavity. Hence, this research aimed to improve PM treatment by evaluating a nanoparticle-loaded, pH-switchable supramolecular polymer hydrogel as a controlled release drug delivery system that can be IP nebulized. Moreover, a multidirectional nozzle was developed to allow nebulization of viscous materials such as hydrogels and to reach an even IP gel deposition. We demonstrated that acidification of the nebulized hydrogelator solution by carbon dioxide, used to inflate the IP cavity during laparoscopic surgery, stimulated the in situ gelation, which prolonged the IP hydrogel retention. In vitro experiments indicated that paclitaxel nanocrystals were gradually released from the hydrogel depot formed, which sustained the cytotoxicity of the formulation for 10 days. Finally, after aerosolization of this material in a xenograft model of PM, tumor progression could successfully be delayed, while the overall survival time was significantly increased compared to non-treated animals.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CO₂-Driven Nebulization of pH-Sensitive Supramolecular Polymers for Intraperitoneal Hydrogel Formation and the Treatment of Peritoneal Metastasis

Braet,

Fransen,

Mariën

et al. 2023

ACS Appl. Mater. Interfaces

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“…Despite their importance, these parameters are probably not attributable to the isolated effect of PIPAC, but to the combined treatment and patient care efforts. Several reviews have been published on PIPAC, but some do not discuss response evaluation, whereas others report on histological response evaluation only [ 1 , 8 ]. They do not touch upon the lack of non-invasive procedures for objective and reliable response evaluation.…”

Section: Introductionmentioning

confidence: 99%

Response Evaluation in Patients with Peritoneal Metastasis Treated with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC)

Roensholdt

Detlefsen

Mortensen

et al. 2023

JCM

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Pressurized intraperitoneal aerosol chemotherapy (PIPAC) directed therapy emerged as a treatment of peritoneal metastasis (PM) a decade ago. The response assessment of PIPAC is not uniform. This narrative review describes non-invasive and invasive methods for response evaluation of PIPAC and summarizes their current status. PubMed and clinicaltrials.gov were searched for eligible publications, and data were reported on an intention-to-treat basis. The peritoneal regression grading score (PRGS) showed a response in 18–58% of patients after two PIPACs. Five studies showed a cytological response in ascites or peritoneal lavage fluid in 6–15% of the patients. The proportion of patients with malignant cytology decreased between the first and third PIPAC. A computed tomography showed stable or regressive disease following PIPAC in 15–78% of patients. The peritoneal cancer index was mainly used as a demographic variable, but prospective studies reported a response to treatment in 57–72% of patients. The role of serum biomarkers of cancer or inflammation in the selection of candidates for and responders to PIPAC is not fully evaluated. In conclusion, response evaluation after PIPAC in patients with PM remains difficult, but PRGS seems to be the most promising response evaluation modality.

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“…For those patients not eligible for CRS and HIPEC, pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new palliative treatment option that is considered safe. Randomized research is needed to confirm its additional value [19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Intraperitoneal drug delivery systems releasing cytostatic agents to target gastro-intestinal peritoneal metastases in laboratory animals: a systematic review

Wintjens

Simkens

Fransen³

et al. 2022

Clin Exp Metastasis

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For peritoneal metastases (PM), there are few curative treatment options, and they are only available for a select patient group. Recently, new therapies have been developed to deliver intraperitoneal chemotherapy for a prolonged period, suitable for a larger patient group. These drug delivery systems (DDSs) seem promising in the experimental setting. Many types of DDSs have been explored in a variety of animal models, using different cytostatics. This review aimed to provide an overview of animal studies using DDSs containing cytostatics for the treatment of gastro-intestinal PM and identify the most promising therapeutic combinations. The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) guidelines. The 35 studies included revealed similar results: using a cytostatic-loaded DDS to treat PM resulted in a higher median survival time (MST) and a lower intraperitoneal tumor load compared to no treatment or treatment with a ‘free’ cytostatic or an unloaded DDS. In 65% of the studies, the MST was significantly longer and in 24% the tumor load was significantly lower in the animals treated with cytostatic-loaded DDS. The large variety of experimental setups made it impossible to identify the most promising DDS-cytostatic combination. In most studies, the risk of bias was unclear due to poor reporting. Future studies should focus more on improving the clinical relevance of the experiments, standardizing the experimental study setup, and improving their methodological quality and reporting.

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The emergence of pressurized intraperitoneal aerosol chemotherapy as a palliative treatment option for patients with diffuse peritoneal metastases: a narrative review

Cited by 16 publications

References 72 publications

CO₂-Driven Nebulization of pH-Sensitive Supramolecular Polymers for Intraperitoneal Hydrogel Formation and the Treatment of Peritoneal Metastasis

CO₂-Driven Nebulization of pH-Sensitive Supramolecular Polymers for Intraperitoneal Hydrogel Formation and the Treatment of Peritoneal Metastasis

Response Evaluation in Patients with Peritoneal Metastasis Treated with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC)

Intraperitoneal drug delivery systems releasing cytostatic agents to target gastro-intestinal peritoneal metastases in laboratory animals: a systematic review

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The emergence of pressurized intraperitoneal aerosol chemotherapy as a palliative treatment option for patients with diffuse peritoneal metastases: a narrative review

Cited by 16 publications

References 72 publications

CO2-Driven Nebulization of pH-Sensitive Supramolecular Polymers for Intraperitoneal Hydrogel Formation and the Treatment of Peritoneal Metastasis

CO2-Driven Nebulization of pH-Sensitive Supramolecular Polymers for Intraperitoneal Hydrogel Formation and the Treatment of Peritoneal Metastasis

Response Evaluation in Patients with Peritoneal Metastasis Treated with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC)

Intraperitoneal drug delivery systems releasing cytostatic agents to target gastro-intestinal peritoneal metastases in laboratory animals: a systematic review

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CO₂-Driven Nebulization of pH-Sensitive Supramolecular Polymers for Intraperitoneal Hydrogel Formation and the Treatment of Peritoneal Metastasis

CO₂-Driven Nebulization of pH-Sensitive Supramolecular Polymers for Intraperitoneal Hydrogel Formation and the Treatment of Peritoneal Metastasis